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1.
Biomaterials ; 312: 122732, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39088913

RESUMEN

Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.


Asunto(s)
Proliferación Celular , MicroARNs , Infarto del Miocardio , Miocitos Cardíacos , Estrés Oxidativo , Animales , MicroARNs/metabolismo , MicroARNs/genética , Miocitos Cardíacos/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Estrés Oxidativo/efectos de los fármacos , Ratones , Porcinos , Hidrogeles/química , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo
2.
Int J Gen Med ; 17: 4407-4418, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355341

RESUMEN

Background and Aims: The red blood cell distribution width (RDW) to albumin (ALB) ratio (RAR) has been identified as a prognostic indicator for mortality in critically ill patients across various diseases. Nevertheless, the impact of RAR on clinical functional prognosis in Acute ischemic stroke (AIS) remains uncertain. This study aimed to evaluate the prognostic significance of RAR in AIS patients. Methods: A secondary analysis was performed on a cohort study, involving 1906 AIS patients recruited from a South Korean academic hospital. Both univariate and multivariate logistic regression was employed to assess the connections between RAR and negative functional results in AIS. To explore potential non-linear relationships in this association, a generalized additive model (GAM) and smooth curve fitting were utilized. Further, a mediation analysis was performed to identify possible mediators. Results: Out of the 1906 eligible patients, 546 (28.65%) were found to have an unfavorable prognosis. Patients with elevated RAR had a higher likelihood of facing a negative prognosis in AIS (all P<0.001). RAR demonstrated a dose-response relationship with the probability of poor functional prognosis. When analysis of RAR as a continuous variable, an increase in RAR was correlated with a higher risk of adverse prognosis.When RAR was analyzed as quartile variables, the highest RAR remained an independent contributing factor for both 3-month unfavorable outcomes (adjusted OR, 1.4; 95% CI: 1.0-2.1, P=0.046) and 3-month mortality (adjusted OR, 5.2; 95% CI, 2.0-13.9; p<0.001). More interestingly, the presence of a pro-inflammatory state may serve as a mediator in the connections between RAR and adverse functional outcomes. Conclusion: Given its cost-effectiveness and ease of measurement, baseline RAR holds promise as a valuable biomarker for early risk assessment in AIS patients.

3.
Life Sci ; : 123086, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39357794

RESUMEN

Peripheral nerve injury (PNI) can cause nerve demyelination, neuronal apoptosis, axonal atrophy, inflammatory infiltration, glial scar formation, and other pathologies that can lead to sensory and motor dysfunction and seriously affect the psychosomatic health of patients. There is currently no effective treatment method, so exploring a promising treatment method is of great significance. Several studies have revealed the therapeutic roles of Schwann cells (SCs) and their exosomes in nerve injury repair. Exosomes are extracellular nanovesicles secreted by cells that act as key molecules in intercellular communication. Progress has been made in understanding the role of exosomes derived from SCs (SC-EXOs) in peripheral nerve regeneration, including the promotion of axonal regeneration and myelin formation, anti-inflammation, vascular regeneration, neuroprotection, and neuroregulation. Therefore, in this paper, we summarize the functional characteristics of SC-EXOs and discuss their potential therapeutic effects on PNI repair as well as some existing problems and future challenges.

4.
Inorg Chem ; 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350542

RESUMEN

A cerium(III)-containing silicotungstate, [H2N(CH3)2]10NaK[KCe(SiW11O39)2(H2O)]·18.5H2O (CeSiW), was successfully synthesized and characterized. Structure analysis reveals that CeSiW is composed of two {SiW11O39} units connected by one cerium(III) cation to form a typical 1:2 sandwich structure, which is further expanding into a 1D chain linked by K+ ions. The oxygen-enriched surfaces of {SiW11O39} units and open cerium sites provide abundant Lewis base and acid sites in CeSiW. As a result, CeSiW efficiently catalyzed the C3-alkenylation of oxindoles with aldehydes through the simultaneous activation of both reaction substrates on its crystal framework. Various 3-benzylidene-oxindoles are synthesized with excellent yields and high E-selectivity under solvent-free conditions.

5.
Antonie Van Leeuwenhoek ; 118(1): 13, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39352515

RESUMEN

An aerobic, Gram-stain negative bacterium was isolated from sediment samples of Barkol salt lake in Hami City, Xinjiang Uygur Autonomous Region, China, with the number EGI_FJ10229T. The strain is ellipse-shaped, oxidase-negative, catalase-positive, and has white, round, smooth, opaque colonies on marine 2216 E agar plate. Growth occurs at 4.0-37.0 â„ƒ (optimal:30.0 â„ƒ), pH 7.0-9.0 (optimal: pH 8.0) and NaCl concentration of 0-8.0% (optimal: 3.0%). Phylogenetic analysis based on 16S rRNA gene and genome sequences indicated that the isolated strain should be assigned to the genus Aquibaculum and was most closely related to Aquibaculum arenosum CAU 1616 T. Average nucleotide identity (ANI) and Average amino-acid identity (AAI) values between the type species of the genus Aquibaculum and other related type species were lower than the threshold values recommended for bacterial species. The genomic DNA G + C content of EGI_FJ10229T was 65.41%. The major polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylcholine, phosphatidylethanolamine and unidentified phospholipid. The major fatty acids (> 5%) were C19:0 cyclo ω8c (42.0%) and C18:1 ω7c (33.78%). The respiratory quinone identified was Q-10. Differential phenotypic and genotypic characteristics of this strain and species of genus Aquibaculum showed that the strain should be classified as representing a new species belonging to this genus, for which the name Aquibaculum sediminis sp. nov. is proposed. The type strain of the proposed novel species is EGI_FJ10229T (= KCTC 8570 T = GDMCC 1.4598 T).


Asunto(s)
Composición de Base , ADN Bacteriano , Sedimentos Geológicos , Lagos , Filogenia , ARN Ribosómico 16S , Sedimentos Geológicos/microbiología , Lagos/microbiología , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , China , Técnicas de Tipificación Bacteriana , Ácidos Grasos/análisis , Cloruro de Sodio/metabolismo , Fosfolípidos/análisis , Análisis de Secuencia de ADN
6.
Front Microbiol ; 15: 1447755, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268535

RESUMEN

This study utilized high-throughput sequencing to investigate endophytic bacteria diversity in halophytic plants Anabasis truncate (AT) and Anabasis eriopoda (AE) from the Aral Sea region. Following sequence processing, 356 Amplicon Sequence Variants (ASVs) were discovered. The abundance and variety of endophytic bacteria were higher in AT. Bacillota, Pseudomonadota, Actinomycetota, and Bacteroidota constituted the dominant in AE, whereas Pseudomonadota, Actinomycetota, Bacteroidota, and Chloroflexota constituted the dominant in AT. Biomarkers were identified through LEFSe analysis, showing host-specific patterns. PCoA indicated distinct bacterial community structures. Phylogenetic analysis revealed diverse endophytic bacteria, including potential novel taxa. PICRUSt2 predicted diverse functions for endophytic bacteria in halophytes, indicating recruitment of beneficial bacterial taxa to adapt to extreme hypersaline conditions, including plant growth-promoting, biocontrol, and halophilic/tolerant bacteria. Moreover, the evolutionary relationship, metabolic capabilities, and plant beneficial potentials of the Bacillus swezeyi strains, previously isolated from the above two halophytes, were analyzed using comparative genomic and physiological analysis. The B. swezeyi strains displayed versatile environmental adaptability, as shown by their ability to use a wide range of carbon sources and their salt tolerances. B. swezeyi possessed a wide range of enzymatic capabilities, including but not limited to proteases, cellulases, and chitinases. Comparative genomic analysis revealed that despite some variations, they shared genetic similarities and metabolic capabilities among the B. swezeyi strains. B. swezeyi strains also displayed outstanding plant-growth-promoting and antagonistic potentials, offering potential solutions to the global food crisis. This study enhances our understanding of microbial diversity in halophytes on saline-alkali land in the West Aral Sea, shedding light on the halophyte microbiome and its collaboration with hosts in highly hypersaline environments. This study also provides a scientific basis for developing high-quality microbial fertilizers and implementing sustainable agricultural practices.

7.
Antonie Van Leeuwenhoek ; 118(1): 4, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269642

RESUMEN

A Gram-stain-negative, aerobic, motile and rod-shaped bacterium, the color of the bacterial colony ranges from light yellow to yellow, designated YC-2023-2T, was isolated from sediment sample of Yuncheng salt lake. Growth occurred at 15-45℃ (optimum 37℃), pH 6.0-9.0 (optimum pH 7.0-8.0) and with 0-8.0% NaCl (w/v, optimum 2.0%). The phylogenetic analysis based on 16S rRNA gene sequences showed that strain YC-2023-2T belonged to the family Kordiimonadaceae. The closely related members were Gimibacter soli 6D33T (92.38%), Kordiimonas lipolytica M41T (91.88%), Eilatimonas milleporae DSM 25217T (91.88%) and Kordiimonas gwangyangensis JCM 12864T (91.84%). The genome of strain YC-2023-2T was 2957513 bp, and the genomic DNA G+C content was 63.91%. The main respiratory quinone was Q-10 and the major fatty acids (>10%) were iso-C15:0, C16:0, C19:0 cyclo ω8c, Summed Feature 8 (C18:1 ω6c or C18:1 ω7c) and Summed Feature 9 (iso-C17:1 ω9c or C16:0 10-methyl). The major polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, unidentified glycolipid, unidentified lipid, and two unidentified aminolipids. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain YC-2023-2T is proposed to represent a novel species of a novel genus named Yunchengibacter salinarum gen. nov., sp. nov., within the family Kordiimonadaceae. The type strain is YC-2023-2T (= GDMCC 1.4502T = KCTC 8546T).


Asunto(s)
Composición de Base , ADN Bacteriano , Ácidos Grasos , Sedimentos Geológicos , Lagos , Filogenia , ARN Ribosómico 16S , Sedimentos Geológicos/microbiología , Lagos/microbiología , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Ácidos Grasos/análisis , Técnicas de Tipificación Bacteriana , China , Análisis de Secuencia de ADN , Cloruro de Sodio/metabolismo
8.
Neuropharmacology ; 261: 110138, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39244013

RESUMEN

When a naïve observer meets with a familiar conspecific in pain, mice may have a myriad of social (sniffing, allolicking, allogrooming, huddling) and non-social (self-grooming) behaviors under dyadic social interaction (DSI) paradigm. Unlike male, female observers express more allolicking behavior toward injury site of a familiar female in pain, but with less body allogrooming. In current study, we investigated roles of natural estrus cycle phases and ovarian estrogen in these behaviors and results showed that: (1) there was no changes in above behaviors in terms of latency, time and bouts across different natural estrus cycle phases in intact female. (2) however, ovariectomy (OVX) changed estrus cycle phases, lowered circulating level of ovarian estrogen, reduced time and bouts of allolicking behavior and increased time of self-grooming without affecting other behaviors. Moreover, OVX in observers decreased social buffering effect of DSI on spontaneous pain-related behavior in demonstrator relative to naïve and sham controls. (3) treatment of OVX-female with ß-estradiol (E2) or progesterone (PROG) as replacement therapies, only E2 reversed impairment of allolicking behavior. (4) Additionally, socially transferred pain could be identified in intact female across all estrus cycle phases post-DSI, but disappeared in OVX-female, which could be reversed completely by E2 but not by PROG. (5) Finally, serum levels of estrogen, PROG, oxytocin, arginine vasopressin (AVP), prolactin, norepinephrine and 5-HT were examined by ELISA after E2, results showed only AVP level was significantly increased. These results suggest both injury site-targeted caring behavior and socially transferred pain are selectively dependent on ovarian estrogen.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39233286

RESUMEN

17α-Ethinylestradiol (EE2) is known for its endocrine-disrupting effects on embryonic and adult fish. However, its impact on juvenile zebrafish has not been well established. In this study, juvenile zebrafish were exposed to EE2 at concentrations of 5 ng/L (low dose, L), 10 ng/L (medium dose, M), and 50 ng/L (high dose, H) from 21 days post-fertilization (dpf) to 49 dpf. We assessed their growth, development, behavior, transcriptome, and metabolome. The findings showed that the survival rate in the EE2-H group was 66.8 %, with all surviving fish displaying stunted growth and swollen, transparent abdomens by 49 dpf. Moreover, severe organ deformities were observed in the gills, kidneys, intestines, and heart of fish in both the EE2-H and EE2-M groups. Co-expression analysis of mRNA and lncRNA revealed that EE2 downregulated the transcription of key genes involved in the cell cycle, DNA replication, and Fanconi anemia signaling pathways. Additionally, metabolomic analysis indicated that EE2 influenced metabolism and development-related signaling pathways. These pathways were also significantly identified based on the genes regulated by lncRNA. Consequently, EE2 induced organ deformities and mortality in juvenile zebrafish by disrupting signaling pathways associated with development and metabolism. The results of this study offer new mechanistic insights into the adverse effects of EE2 on juvenile zebrafish based on multiomics analysis. The juvenile zebrafish are highly sensitive to EE2 exposure, which is not limited to adult and embryonic stages. It is a potential model for studying developmental toxicity.


Asunto(s)
Etinilestradiol , Contaminantes Químicos del Agua , Pez Cebra , Animales , Etinilestradiol/toxicidad , Contaminantes Químicos del Agua/toxicidad , Disruptores Endocrinos/toxicidad , Transcriptoma/efectos de los fármacos , Multiómica
10.
J Intensive Care ; 12(1): 35, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294818

RESUMEN

BACKGROUND: The optimal sedative regime for noninvasive ventilation (NIV) intolerance remains uncertain. The present study aimed to assess the efficacy and safety of remifentanil (REM) compared to dexmedetomidine (DEX) in cardiac surgery patients with moderate-to-severe intolerance to NIV. METHODS: In this multicenter, prospective, single-blind, randomized controlled study, adult cardiac surgery patients with moderate-to-severe intolerance to NIV were enrolled and randomly assigned to be treated with either REM or DEX for sedation. The status of NIV intolerance was evaluated using a four-point NIV intolerance score at different timepoints within a 72-h period. The primary outcome was the mitigation rate of NIV intolerance following sedation. RESULTS: A total of 179 patients were enrolled, with 89 assigned to the REM group and 90 to the DEX group. Baseline characteristics were comparable between the two groups, including NIV intolerance score [3, interquartile range (IQR) 3-3 vs. 3, IQR 3-4, p = 0.180]. The chi-squared test showed that mitigation rate, defined as the proportion of patients who were relieved from their initial intolerance status, was not significant at most timepoints, except for the 15-min timepoint (42% vs. 20%, p = 0.002). However, after considering the time factor, generalized estimating equations showed that the difference was statistically significant, and REM outperformed DEX (odds ratio = 3.31, 95% confidence interval: 1.35-8.12, p = 0.009). Adverse effects, which were not reported in the REM group, were encountered by nine patients in the DEX group, with three instances of bradycardia and six cases of severe hypotension. Secondary outcomes, including NIV failure (5.6% vs. 7.8%, p = 0.564), tracheostomy (1.12% vs. 0%, p = 0.313), ICU LOS (7.7 days, IQR 5.8-12 days vs. 7.0 days, IQR 5-10.6 days, p = 0.219), and in-hospital mortality (1.12% vs. 2.22%, p = 0.567), demonstrated comparability between the two groups. CONCLUSIONS: In summary, our study demonstrated no significant difference between REM and DEX in the percentage of patients who achieved mitigation among cardiac surgery patients with moderate-to-severe NIV intolerance. However, after considering the time factor, REM was significantly superior to DEX. Trial registration ClinicalTrials.gov (NCT04734418), registered on January 22, 2021. URL of the trial registry record: https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000AM4S&selectaction=Edit&uid=U00038YX&ts=3&cx=eqn1z0 .

11.
Neurochem Int ; 180: 105862, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307461

RESUMEN

BACKGROUND: Fibrotic scar formation is a critical pathological change impacting tissue reconstruction and functional recovery after ischemic stroke. The regulatory mechanisms behind fibrotic scarring in the central nervous system (CNS) remain largely unknown. While macrophages are known to play a role in fibrotic scar formation in peripheral tissues, the involvement of microglia, the resident immune cells of the CNS, in CNS fibrosis requires further exploration. The Sonic Hedgehog (Shh) signaling pathway, pivotal in embryonic development and tissue regeneration, is also crucial in modulating fibrosis in peripheral tissues. However, the impact and regulatory mechanisms of Shh on fibrotic scar formation post-ischemic stroke have not been thoroughly investigated. METHODS: This study explores whether Shh can regulate fibrotic scar formation post-ischemic stroke and its underlying mechanisms through in vivo and in vitro manipulation of Shh expression. RESULTS: Our results showed that Shh expression was upregulated in the serum of acute ischemic stroke patients, as well as in the serum, CSF, and ischemic regions of MCAO/R mice. Moreover, the upregulation of Shh expression was positively correlated with fibrotic scar formation and M2 microglial polarization. Shh knockdown inhibited fibrotic scar formation and M2 microglial polarization while aggravating neurological deficits in MCAO/R mice. In vitro, adenoviral knockdown or Smoothened Agonist (SAG) activation of Shh expression in BV2 cells following OGD/R regulated their polarization and influenced the expression of TGFß1 and PDGFA, subsequently affecting fibroblast activation. CONCLUSION: These results suggest that Shh regulates M2 microglial polarization and fibrotic scar formation after cerebral ischemia.

12.
Transl Psychiatry ; 14(1): 396, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39349463

RESUMEN

Depression is a significant mental health issue with extensive economic implications, and recent studies suggest it may be transmitted between individuals. However, the mechanisms of this contagion remain unclear, and the social buffering effect has been understudied. This research employs three rodent models, including stress crossover, cohabitation-induced, and non-contact induced depression contagion models, to explore these mechanisms. Here, we report that that naive mice cohabiting with depressed mice showed increased corticosterone levels and depressive behaviors, unlike those with stressed mice, who did not exhibit these changes and even mitigated desperation in stressed mice. Non-contact cohabitation did not produce significant behavioral differences, but exposure to bedding from depressed mice reduced sucrose preference in naive mice. This study introduces reliable models of depression contagion, suggesting it operates independently of stress transmission. The interplay between depression contagion and social buffering may vary in different contexts. These findings provide new insights into the mechanisms of depression contagion and potential strategies for preventing depressive disorders.


Asunto(s)
Conducta Animal , Corticosterona , Depresión , Modelos Animales de Enfermedad , Estrés Psicológico , Animales , Ratones , Masculino , Corticosterona/sangre , Depresión/psicología , Estrés Psicológico/psicología , Ratones Endogámicos C57BL , Conducta Social , Trastorno Depresivo/psicología
13.
JAMA ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292480
14.
Sci Total Environ ; 952: 175879, 2024 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-39233068

RESUMEN

There is an association between noise exposure and cognitive impairment, and noise may have a more severe impact on patients with Alzheimer's disease (AD) and mild cognitive impairment; however, the mechanisms need further investigation. This study used the classic AD animal model APP/PS1 mice to simulate the AD population, and C57BL/6J mice to simulate the normal population. We compared their cognitive abilities after noise exposure, analyzed changes in Cluster of Differentiation (CD) between the two types of mice using transcriptomics, identified the differential CD molecule: CD36 in APP/PS1 after noise exposure, and used its pharmacological inhibitor to intervene to explore the mechanism by which CD36 affects APP/PS1 cognitive abilities. Our study shows that noise exposure has a more severe impact on the cognitive abilities of APP/PS1 mice, and that the expression trends of differentiation cluster molecules differ significantly between C57BL/6J and APP/PS1 mice. Transcriptomic analysis showed that the expression of CD36 in the hippocampus of APP/PS1 mice increased by 2.45-fold after noise exposure (p < 0.001). Meanwhile, Western Blot results from the hippocampus and entorhinal cortex indicated that CD36 protein levels increased by approximately 1.5-fold (p < 0.001) and 1.3-fold (p < 0.05) respectively, after noise exposure in APP/PS1 mice. The changes in CD36 expression elevated oxidative stress levels in the hippocampus and entorhinal cortex, leading to a decrease in PI3K/AKT phosphorylation, which in turn increased M1-type microglia and A1-type astrocytes while reducing the numbers of M2-type microglia and A2-type astrocytes. This increased neuroinflammation in the hippocampus and entorhinal cortex, causing synaptic and neuronal damage in APP/PS1 mice, ultimately exacerbating cognitive impairment. These findings may provide new insights into the relationship between noise exposure and cognitive impairment, especially given the different expression trends of CD molecules in the two types of mice, which warrants further research.


Asunto(s)
Antígenos CD36 , Disfunción Cognitiva , Ratones Endogámicos C57BL , Ruido , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Ratones , Antígenos CD36/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ruido/efectos adversos , Fosfatidilinositol 3-Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Enfermedad de Alzheimer/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Ratones Transgénicos
15.
Front Psychol ; 15: 1394309, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39323581

RESUMEN

Previous research on the perception of segmental features of languages has established a correlation between the phoneme inventory of a language and its speakers' perceptual abilities, as indexed by discrimination tasks and Mismatch Negativity (MMN). Building on this background, the current study elucidated the relationship between perceptual ability and tonal inventory by utilizing two tonal languages. Two groups of participants were included in the present experiment: Mandarin speakers and Hakka-Mandarin speakers. Onset latency analysis revealed a significant difference in the Mandarin syllable condition, with Hakka-Mandarin speakers demonstrating earlier MMN latency than Mandarin speakers. This suggests a more efficient auditory processing mechanism in Hakka-Mandarin speakers. Both groups, however, showed similar MMN latency in the Hakka syllable condition. The interaction between language background and syllable type indicates that other factors, such as syllable sonority, also influence MMN responses. These findings highlight the importance of considering multiple phonemic inventories and syllable characteristics in studies of tonal perception.

16.
Genes (Basel) ; 15(9)2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39336805

RESUMEN

The genetic basis of schizophrenia (SZ) remains elusive despite its characterization as a highly heritable disorder. This incomplete understanding has led to stagnation in therapeutics and treatment, leaving many suffering with insufficient relief from symptoms. However, recent large-cohort genome- and exome-wide association studies have provided insights into the underlying genetic machinery. The scale of these studies allows for the identification of ultra-rare mutations that confer substantial disease risk, guiding clinicians and researchers toward general classes of genes that are central to SZ etiology. One such large-scale collaboration effort by the Schizophrenia Exome Sequencing Meta-Analysis consortium identified ten, high-risk, ultra-rare, protein-truncating variants, providing the clearest picture to date of the dysfunctional gene products that substantially increase risk for SZ. While genetic studies of SZ provide valuable information regarding "what" genes are linked with the disorder, it is an open question as to "when" during brain development these genetic mutations impose deleterious effects. To shed light on this unresolved aspect of SZ etiology, we queried the BrainSpan developmental mRNA expression database for these ten high-risk genes and discovered three general expression trajectories throughout pre- and postnatal brain development. The elusiveness of SZ etiology, we infer, is not only borne out of the genetic heterogeneity across clinical cases, but also in our incomplete understanding of how genetic mutations perturb neurodevelopment during multiple critical periods. We contextualize this notion within the National Institute of Mental Health's Research Domain Criteria framework and emphasize the utility of considering both genetic variables and developmental context in future studies.


Asunto(s)
Predisposición Genética a la Enfermedad , Mutación , Esquizofrenia , Esquizofrenia/genética , Humanos , Variación Genética , Estudio de Asociación del Genoma Completo , Encéfalo/patología , Encéfalo/metabolismo , Secuenciación del Exoma/métodos
17.
Bioengineering (Basel) ; 11(9)2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39329635

RESUMEN

Anoikis is a distinct type of programmed cell death and a unique mechanism for tumor progress. However, its exact function in gastric cancer (GC) remains unknown. This study aims to investigate the function of anoikis-related lncRNA (ar-lncRNA) in the prognosis of GC and its immunological infiltration. The ar-lncRNAs were derived from RNA sequencing data and associated clinical information obtained from The Cancer Genome Atlas. Pearson correlation analysis, differential screening, LASSO and Cox regression were utilized to identify the typical ar-lncRNAs with prognostic significance, and the corresponding risk model was constructed, respectively. Comprehensive methods were employed to assess the clinical characteristics of the prediction model, ensuring the accuracy of the prediction results. Further analysis was conducted on the relationship between immune microenvironment and risk features, and sensitivity predictions were made about anticancer medicines. A risk model was built according to seven selected ar-lncRNAs. The model was validated and the calibration plots were highly consistent in validating nomogram predictions. Further analyses revealed the great accuracy of the model and its ability to serve as a stand-alone GC prognostic factor. We subsequently disclosed that high-risk groups display significant enrichment in pathways related to tumors and the immune system. Additionally, in tumor immunoassays, notable variations in immune infiltrates and checkpoints were noted between different risk groups. This study proposes, for the first time, that prognostic signatures of ar-lncRNA can be established in GC. These signatures accurately predict the prognosis of GC and offer potential biomarkers, suggesting new avenues for basic research, prognosis prediction and personalized diagnosis and treatment of GC.

18.
Microorganisms ; 12(9)2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39338558

RESUMEN

Burkholderia (sensu lato) is a diverse group of ß-Proteobacteria that exists worldwide in various environments. The SBE clade of this group was thought to be mutualistic with stinkbugs. Riptortus-Burkholderia was suggested as an ideal model system for studying insect-microbe symbiosis. To explore the strain-level diversity of Burkholderia at the individual and population levels of Riptortus stinkbugs (Hemiptera: Alydidae), and to uncover the factors affecting the Burkholderia community, large-scale sampling of two Riptortus species and deep sequencing data (16S amplicon) were used in the present study. Our results showed that: (1) the proportions of facultative symbiotic bacteria Burkholderia were very high, with an average proportion of 87.1% in the samples; (2) only six out of 1373 Burkholderia amplicon sequence variants (ASVs) did not belong to the SBE clade, accounting for only 0.03% of Burkholderia; (3) a relatively small number of Burkholderia ASVs had a large number of sequences, with 22, 54, and 107 ASVs accounting for more than 1.0%, 0.1%, and 0.01% of the total Burkholderia sequences, respectively; (4) multiple Burkholderia ASVs were present in most Riptortus individuals, but there was one dominant or two codominant ASVs, and codominance was more likely to occur when the genetic distance between the two codominant ASVs was small; and (5) the beta diversity of Burkholderia was significantly different between the two host species (PerMANOVA: both Jaccard and Bray-Curtis, p < 0.001) and among localities (PerMANOVA: both Jaccard and Bray-Curtis, p < 0.001). Two-way PerMANOVA also indicated that both the host (Bray-Curtis, p = 0.020; Jaccard, p = 0.001) and geographical location (Bray-Curtis, p = 0.041; Jaccard, p = 0.045) influence Burkholderia communities; furthermore, Mantel tests showed that the Burkholderia communities were significantly correlated with the geographical distance of sample locations (R = 0.056, p = 0.001). Together, our findings demonstrate the fine-scale diversity of Burkholderia symbionts and suggest a region- and host-dependent pattern of Burkholderia in Riptortus stinkbugs.

19.
Neuroscience ; 560: 120-129, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39307415

RESUMEN

Direct or indirect injury of peripheral nerve can lead to sensory and motor dysfunction, which can lead to pathological pain and seriously affect the quality of life and psychosomatic health of patients. While the internal repair function of the body after peripheral nerve injury is limited. Nerve regeneration is the key factor hindering the recovery of nerve function. At present, there is no effective treatment. Therefore, more and more attention have been paid to the development of foreground treatment to achieve functional recovery after peripheral nerve injury, including relief of pathological pain. Cell transplantation strategy is a therapeutic method with development potential in recent years, which can exert endogenous alternative repair by transplanting exogenous functional bioactive cells to the site of nerve injury. Olfactory ensheathing cells (OECs) are a special kind of glial cells, which have the characteristics of continuous renewal and survival. The mechanisms of promoting nerve regeneration and functional repair and relieving pathological pain by transplantation of OECs to peripheral nerve injury include secretion of a variety of neurotrophic factors, axonal regeneration and myelination, immune regulation, anti-inflammation, neuroprotection, promotion of vascular growth and improvement of inflammatory microenvironment around nerve injury. Different studies have shown that OECs combined with biomaterials have made some progress in the treatment of peripheral nerve injury and pathological pain. These biomaterials enhance the therapeutic effect of OECs. Therefore, the functional role of OECs in peripheral nerve injury and pathological pain was discussed in this paper.Although OECs are in the primary stage of exploration in the repair of peripheral nerve injury and the application of pain, but OECs transplantation may become a prospective therapeutic strategy for the treatment of peripheral nerve injury and pathological pain.

20.
Microbiol Res ; 289: 127915, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39342746

RESUMEN

In the context of growing antibiotic resistance in bacteria, the quorum-sensing (QS) system of Pseudomonas aeruginosa (P. aeruginosa) has become a target for new therapeutic strategies. QS is a crucial communication process and an essential pathogenic mechanism. This comprehensive review explores the critical role of QS in the pathogenesis of P. aeruginosa infections, including lung, burn, bloodstream, gastrointestinal, corneal, and urinary tract infections. In addition, this review delves into the complexity of the bacterial QS communication network and highlights the intricate mechanisms underlying these pathological processes. Notably, in addition to the four main QS systems, bacterial QS can interact with various external and internal signaling networks, such as host environments and nutrients in the external microbiome, as well as internal virulence regulation systems within bacteria. These elements can significantly influence the behavior and virulence of microbial communities. Therefore, this review reveals that inhibitors targeting singular QS pathways may inadvertently promote virulence in other pathways, leading to new trends in drug resistance. In response to evolving resistance challenges, this study proposes more cautious treatment strategies, including multitarget interventions and combination therapies, aimed at combating the escalating issue of resistance.

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